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Heterogeneity of human bone marrow and blood natural killer cells defined by single-cell transcriptome

2019; Nature Portfolio; Volume: 10; Issue: 1 Linguagem: Inglês

10.1038/s41467-019-11947-7

2041-1723

Chao Yang, Jason Siebert, Robert Burns, Zachary J. Gerbec, Benedetta Bonacci, Amy L. Rymaszewski, Mary Rau, Matthew J. Riese, Sridhar Rao, Karen-Sue Carlson, John M. Routes, James Verbsky, Monica S. Thakar, Subramaniam Malarkannan,

Immune cells in cancer

Abstract Natural killer (NK) cells are critical to both innate and adaptive immunity. However, the development and heterogeneity of human NK cells are yet to be fully defined. Using single-cell RNA-sequencing technology, here we identify distinct NK populations in human bone marrow and blood, including one population expressing higher levels of immediate early genes indicative of a homeostatic activation. Functionally matured NK cells with high expression of CX3CR1 , HAVCR2 (TIM-3), and ZEB2 represents terminally differentiated status with the unique transcriptional profile. Transcriptomic and pseudotime analyses identify a transitional population between CD56 bright and CD56 dim NK cells. Finally, a donor with GATA2 T354M mutation exhibits reduced percentage of CD56 bright NK cells with altered transcriptome and elevated cell death. These data expand our understanding of the heterogeneity and development of human NK cells.